Itch-specific brain circuit and dopaminergic gene polymorphisms influencing individual differences in itch perception

瘙痒特异性脑回路和多巴胺能基因多态性影响瘙痒感知的个体差异

• 批准号: 10735592
• 负责人: Hideki Mochizuki
• 金额: $ 33.44万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735592
• 关键词: Achievement; Affect; Alleles; Area; Binding; Brain; Brain Stem; Brain imaging; Brain region; Corpus striatum structure; Development; Disease; Dopamine; Dopamine D1 Receptor; Dopamine D2 Receptor; Dorsal; Esthesia; Etiology; Functional Magnetic Resonance Imaging; Genes; Genetic; Genetic Polymorphism; Genotype; Human; Individual Differences; Investigation; Location; Methods; Motivation; Motor; Neurotransmitters; Pain; Participant; Pathway interactions; Patients; Perception; Persons; Play; Prefrontal Cortex; Pruritus; Reporting; Research Project Grants; Research Proposals; Role; Signal Transduction; Spinal; Stimulus; Thalamic structure; Vertebral column; Work; brain based; chronic itch; genetic information; global health; imaging study; novel; pain sensation; success; therapeutic target

Abstract Itch is a global health problem, affecting tens of millions of people. The brain plays a crucial role in itch perception; thus the specific circuit for itch processing in the brain has the potential to become a therapeutic target for itch in a wide range of pruritic diseases. Our understanding about the brain mechanism of itch has advanced in the past decades. Previous studies identified a key brain circuit related to itch, which includes the ascending pathway projecting from the thalamus to the posterior insular cortex (pIC) and networks originating from the pIC. In addition, dopamine was found to be a key neurotransmitter associated with itch. These achievements have also identified two important topics that must be understood to develop effective itch treatment targeting the brain. First, the brain circuit of itch is similar to that of pain, though itch and pain are clearly distinct sensations. An itch-specific ascending pathway and network have not yet been identified within the circuit (an itch-specific circuit). Second, there could be dopaminergic gene polymorphisms that determine individual differences in itch perception. If such polymorphisms are identified, brain imaging studies focusing on these genes can identify key loci regulating itch perception within the itch-specific circuit. This line of work will eventually enable us to develop brain-based, tailored itch treatment. To this end, it is crucial to identify an itch- specific circuit and dopaminergic gene polymorphisms influencing individual differences in itch perception. Our research proposal will address this significant gap. Aims 1 and 2 will use fMRI to determine an itch-specific ascending pathway and network by comparing brain activity between itch and pain stimuli. Aim 3 will use our novel method for quantitatively assessing genetic impacts on itch to identify dopaminergic gene polymorphisms that influence individual differences in itch perception. Success of our project will eventually lead to the development of brain-based tailored itch treatment, which will advance the treatment of chronic itch regardless of the underlying etiology.

抽象的 瘙痒是一个全球健康问题，影响了数千万人。大脑在瘙痒中起着至关重要的作用 洞察力;因此，大脑瘙痒处理的特定电路具有成为治疗性的潜力 瘙痒的靶标在广泛的核疾病中。我们对瘙痒的大脑机制的理解 在过去的几十年中。先前的研究确定了与瘙痒有关的关键脑电路，其中包括 从丘脑向后岛岛的皮层（PIC）和发起的网络投射的上升途径 从图片中。此外，发现多巴胺是与瘙痒相关的关键神经递质。这些 成就还确定了必须理解的两个重要主题，以发展有效的痒 针对大脑的治疗。首先，瘙痒的大脑回路与疼痛相似，尽管瘙痒和疼痛是 明显不同的感觉。在内部尚未识别出瘙痒特定的上升途径和网络 电路（特定于瘙痒的电路）。其次，可能存在确定的多巴胺能基因多态性 瘙痒感的个体差异。如果确定了这种多态性，则大脑成像研究的重点是 这些基因可以识别关键基因座调节瘙痒特异性电路中的瘙痒感。这项工作将 最终使我们能够开发基于大脑的，定制的瘙痒治疗。为此，识别瘙痒至关重要 特定的电路和多巴胺能基因多态性影响瘙痒感的个体差异。我们的 研究建议将解决这一重大差距。目标1和2将使用fMRI来确定特定于瘙痒的特定 通过比较瘙痒和疼痛刺激之间的大脑活动来升高途径和网络。 AIM 3将使用我们的 定量评估对瘙痒的遗传影响以鉴定多巴胺能基因多态性的新方法 这会影响瘙痒感的个体差异。我们项目的成功最终将导致 开发基于大脑的瘙痒症治疗，这将推动慢性瘙痒的治疗 基础病因。